Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro

Journal of Ovarian Research

Congjian Xu³  Yufang Zheng²  Jiabing Zhou¹  Jun Chen⁴  Xiaoyan Zhang¹  Shanshan Hong¹ 

[1] Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, People’s Republic of China;School of Life Sciences, Fudan University, Shanghai 200433, People’s Republic of China;Institute of Biomedical Sciences, Fudan University, Shanghai 200032, People’s Republic of China;Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People’s Republic of China

关键词: Nanoparticle;    Short interfering RNA;    Growth-regulated oncogene α;    Follicle-stimulating hormone;    Targeted therapy;    Ovarian carcinoma;   

Others  :  805011
DOI  :  10.1186/1757-2215-6-80

 received in 2013-09-12, accepted in 2013-11-18,  发布年份 2013

【 摘 要 】

Background

RNA interference technology has shown high therapeutic potential for cancer treatment. However, serum instability, poor tissue permeability and non-specific uptake of short interfering RNA (siRNA) limit its administration in vivo. To overcome these limitations and improve the specificity for ovarian cancer, we developed a targeted nanoparticle delivery system for siRNA. This system included follicle-stimulating hormone (FSH) β 33–53 peptide as a targeting moiety that specifically recognized FSH receptor (FSHR) expressed on ovarian cancer cells. Growth regulated oncogene α (gro-α) has been reported to be involved in ovarian cancer development and progression. Thus, siRNA targeted to gro-α was used as an antitumor drug in this delivery system.

Methods

FSH β 33–53 peptide-conjugated gro-α siRNA-loaded polyethylene glycol (PEG)-polyethylenimine (PEI) nanoparticles (FSH33-G-NP) were prepared and characterized by gel retardation assay and transmission electron microscopy. Particle size and zeta potential were determined. Expression of gro-α mRNA and protein was detected by real-time quantitative RT-PCR, immunocytochemistry and enzyme-linked immunosorbent assay. The proliferation, migration and invasion of the ovarian clear cell carcinoma cell line ES-2 were evaluated by cell counting kit-8 assay, cell scratch assay and transwell migration assay.

Results

A siRNA sequence that is effective in silencing gro-α expression was obtained and loaded into the targeted delivery system. Compared with gro-α siRNA-loaded nanoparticles without FSH peptide modification (G-NP), FSH33-G-NP significantly down-regulated gro-α expression in ES-2 cells at mRNA and protein levels. Consequently, the aggressive biological behaviors of ES-2 cells, including proliferation, migration and invasion, were suppressed after silencing gro-α expression, and the addition of the FSH β 33–53 peptide enhanced the suppressive effects.

Conclusions

This study indicated that a FSHR-mediated delivery system could mediate the highly selective delivery of siRNA into ovarian cancer cells and that silencing gro-α expression could be a potential choice for ovarian cancer treatment.

【 授权许可】

   
2013 Hong et al.; licensee BioMed Central Ltd.

【 图 表 】

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